rs1173107097

Variant names:

• chr7-2355069-G-A
• rs1173107097
• NM_001037283.2:c.148G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001037283.2(EIF3B):​c.148G>A​(p.Ala50Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,257,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: EIF3B NM_001037283.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.531
• Publications: 0 publications found

Genes affected

EIF3B (HGNC:3280): (eukaryotic translation initiation factor 3 subunit B) Enables RNA binding activity. Contributes to translation initiation factor activity. Involved in several processes, including IRES-dependent viral translational initiation; translational initiation; and viral translational termination-reinitiation. Located in extracellular exosome. Part of eukaryotic translation initiation factor 3 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06343588).
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037283.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	NM_001037283.2	MANE Select	c.148G>A	p.Ala50Thr	missense	Exon 1 of 19	NP_001032360.1	P55884-1
	EIF3B	NM_001362791.2		c.148G>A	p.Ala50Thr	missense	Exon 1 of 19	NP_001349720.1	P55884-1
	EIF3B	NM_003751.4		c.148G>A	p.Ala50Thr	missense	Exon 1 of 19	NP_003742.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EIF3B	ENST00000360876.9	TSL:1 MANE Select	c.148G>A	p.Ala50Thr	missense	Exon 1 of 19	ENSP00000354125.4	P55884-1
	EIF3B	ENST00000397011.2	TSL:1	c.148G>A	p.Ala50Thr	missense	Exon 1 of 19	ENSP00000380206.2	P55884-1
	EIF3B	ENST00000899983.1		c.148G>A	p.Ala50Thr	missense	Exon 1 of 19	ENSP00000570042.1

Frequencies

GnomAD3 genomes AF: 0.0000331 AC: 5 AN: 150876 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.0000117 AC: 13 AN: 1106400 Hom.: 0 Cov.: 29 AF XY: 0.0000132 AC XY: 7 AN XY: 528750

African (AFR) AF: 0.00 AC: 0 AN: 22620

American (AMR) AF: 0.00 AC: 0 AN: 8148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14400

East Asian (EAS) AF: 0.00 AC: 0 AN: 25764

South Asian (SAS) AF: 0.00 AC: 0 AN: 31092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2954

European-Non Finnish (NFE) AF: 0.0000128 AC: 12 AN: 934270

Other (OTH) AF: 0.0000226 AC: 1 AN: 44206

GnomAD4 genome AF: 0.0000331 AC: 5 AN: 150876 Hom.: 0 Cov.: 32 AF XY: 0.0000407 AC XY: 3 AN XY: 73700

African (AFR) AF: 0.00 AC: 0 AN: 41272

American (AMR) AF: 0.00 AC: 0 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67576

Other (OTH) AF: 0.000484 AC: 1 AN: 2068

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.97
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.53
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.028
Sift	Benign	0.46	T
Sift4G	Benign	0.20	T
Polyphen		0.0080	B
Vest4		0.078
MutPred		0.11		Gain of phosphorylation at A50 (P = 0.0261)
MVP		0.32
MPC		0.36
ClinPred		0.070	T
GERP RS		2.4
PromoterAI		-0.18	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1
Varity_R		0.017
gMVP		0.22
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1173107097; hg19: chr7-2394704;